Ornithine decarboxylase (ODC) EC 4.1.1.17) catalzyes the synthesis of putrescine; this serves as the common diamine component of spermidine and spermine. ODC is present in all cell types and induction of ODC activity occurs under a variety of conditions associated with growth. We have shown that neuroblastoma, L1210, P388, H-35 cells, as well as 3T3 fibroblasts in culture and rat liver cells have available to them a number of mechanisms to regulate ODC activity in a very sensitive manner. The research of our laboratory has defined a unique mechanism of control of ODC activity. The end products of the reaction elicit the appearance of a specific small molecular weight protein, ODC antizyme, which is a non-competitive inhibitor of ODC and forms a salt-dissociable complex with ODC. It is proposed: (a) to purify and characterize the ODC antizyme and its mode of regulation of ODC activity; (b) to define the intracellular complexes that it forms with ODC; (c) to define how the antizyme interacts with other factors that are co-induced in the cell; (d) to determine the minimal requirements, as well as the discrete steps involved in the induction of ODC and of the ODC antizyme.